Recent evidence in humans and laboratory animals indicates that the interval between implantation and organogenesis, commonly known as gastrulation, may be a period of high teratogenic susceptibility. This study was carried out to evaluate the vulnerability of this developmental period in the nonhuman primate by administering a known teratogen, the alkylating agent cyclophosphamide (CP). In macaques, the gastrulation period is relatively long when compared to other laboratory animals, spanning approximately gestational days (GD) 10-20. CP was orally administered to long-tailed monkeys (Macaca fascicularis) at doses ranging from 1.75 to 7.0 mg/kg/day on GD 16-18. Dose-related embryolethality was the most common outcome and averaged 50% (8/16) for all treated pregnancies. Embryos in the two highest dose groups (3.5 and 7.0 mg/kg) exhibited delayed and/or abnormal in utero growth profiles as detected by ultrasound. Histological evaluation of dying embryos, removed by hysterotomy, revealed widespread necrosis of the neuroepithelium, limb and pharyngeal arch mesenchyme. Surviving infants (n=8) were morphologically normal, although two were growth-retarded. CP teratogenicity was verified by treatment during early organogenesis (GD 27-29) with 7.0 mg/kg, and all four term infants displayed abnormal development similar to that reported in CP-exposed human infants. This included growth retardation as well as cardiac, skeletal and craniofacial abnormalities. This study indicates that the long-tailed macaque is susceptible to the embryolethal, but not teratogenic effects of CP when exposure is restricted to the period of gastrulation.